金黃色葡萄球菌母嬰傳播風(fēng)險的前瞻性隊列研究
發(fā)布時間：2018-07-28 15:50
【摘要】：目的探討孕婦(陰道)及其新生兒(口腔、眼周、耳內(nèi)及臍周)金黃色葡萄球菌(Staphylococcus aureus,以下簡稱SA)的攜帶率,探究SA的藥物敏感性和分子學(xué)特征,研究母嬰SA的同源性并預(yù)測母嬰傳播的風(fēng)險,為有效的防控措施提供科學(xué)依據(jù)。方法本研究采用前瞻性隊列研究和分子流行病學(xué)相結(jié)合的方法,方便抽樣入院待產(chǎn)的孕婦為研究對象并進行隨訪。根據(jù)孕婦的陰道分泌物結(jié)果把孕婦分為暴露組(陰道分泌物分離鑒定出SA陽性)和非暴露組(陰道分泌物分離鑒定出SA陰性),觀察結(jié)局為其新生兒出生時是否攜帶SA。比較兩組中新生兒SA的攜帶率和計算相對危險比(relative risk,RR);SA的藥物敏感性分析使用Kirby-Bauer test紙片擴散法,耐甲氧西林金黃色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)菌株的進一步鑒定使用紙片擴散法和mecA基因擴增法;用t檢驗、χ2檢驗或Fisher確切概率法比較不同組別人群情況的差異、探究新生兒攜帶SA和MRSA的危險因素和菌株藥敏性的差別,單因素分析P0.05的影響因素納入廣義線性模型進行多因素分析;Kappa檢驗分析母嬰SA的表型和毒素基因特征的一致性;應(yīng)用PCR技術(shù)檢測毒素基因(PVL、TST、ETA和ETB),MRSA菌株進一步SCCmec分子分型;使用多位點測序分型(multilocus sequencing typing,MLST)探究本地流行的SA類型并確定母嬰SA的同源性。結(jié)果基本情況:本研究共納入了1834名待產(chǎn)孕婦,其中暴露組孕婦(SA陽性)133人,非暴露組孕婦(SA陰性)1701人。隨訪后共獲得1834個新生兒樣本。SA及MRSA攜帶情況:1834名孕婦中,133人(7.25%)攜帶SA,31人(1.69%)攜帶MRSA。1834名新生兒中,60人(3.27%)攜帶SA,15人(0.82%)攜帶MRSA。暴露組新生兒SA攜帶率為15.79%,MRSA為2.26%;非暴露組新生兒SA攜帶率為2.29%,MRSA為0.71%。兩人群新生兒SA攜帶率有差異,MRSA攜帶率無差異。暴露組新生兒攜帶SA的相對危險比是非暴露組的6.89倍(95%CI:4.18-11.36),調(diào)整新生兒的性別、分娩方式、是否胎膜早破及懷孕天數(shù)影響因素后,暴露組新生兒攜帶SA的相對危險比是非暴露組的6.90倍(95%CI:4.22-11.27)。共有21對母嬰同時檢出SA陽性。藥敏試驗:孕婦SA對克林霉素(41.35%)、紅霉素(50.38%)、替考拉寧(81.20%)和青霉素(92.48%)的耐藥率均較高;與甲氧西林敏感金黃色葡萄球菌(methicillin-susceptible Staphylococcus aureus,MSSA)菌株相比,MRSA是多重耐藥的危險因素(OR=3.64;95%CI:1.23-13.02)。新生兒SA對克林霉素(28.33%)、紅霉素(46.67%)和青霉素(93.33%)的耐藥率較高;MRSA是多重耐藥的危險因素(OR=12.36;95%CI:2.56-76.77)。暴露組與非暴露組新生兒中SA的藥敏情況無差異。21對母嬰配對子耐藥譜一致性有統(tǒng)計學(xué)差異(P0.01),一致性程度為適中(Kappa=0.523)。毒素基因:孕婦中SA的PVL、ETA、ETB和TST基因攜帶率為2.26%、3.01%、0.00%和2.26%,新生兒分別為5.00%、3.33%、11.67%和0.00%。孕婦及新生兒中MRSA與MSSA攜帶PVL、TST、ETA基因的情況均無差異。21對母嬰配對子中,母親及其新生兒中的SA均檢不出PVL和ETB基因,母嬰配對子攜帶TST和ETA基因的一致性有統(tǒng)計學(xué)意義,一致性程度分別為最佳(Kappa=1.000)和適中(Kappa=0.462)。SCCmec分型:孕婦分離的MRSA菌株中,45.16%(14/31)屬于醫(yī)院相關(guān)MRSA(hospital-associated MRSA,HA-MRSA),29.03%(9/31)屬于社區(qū)相關(guān)MRSA(community-associated MRSA,CA-MRSA),以SCCmecⅡ型(11/31)和Ⅳa型(7/31)占優(yōu)。新生兒MRSA中,20.00%(3/15)屬于HA-MRSA,26.67%(4/15)屬于CA-MRSA,以SCCmecⅣa型(4/7)和Ⅱ型(2/7)占優(yōu)。孕婦及新生兒中的HA-MRSA和CA-MRSA菌株對克林霉素、紅霉素和青霉素等抗生素的耐藥性均較高,對11種藥物的耐藥性和多重耐藥無統(tǒng)計學(xué)差異。21對母嬰配對子中,檢出1對MRSA菌株,同為SCCmecⅡ型。MLST:孕婦及新生兒中SA主要的ST型別均為ST188(37/133;15/60)、ST7(18/133;7/60)和ST6(14/133;5/60);MRSA菌株的主要型別均為ST59(8/31;4/15)、ST6(6/31;2/15)和ST188(5/31;3/15)。孕婦及新生兒中SA的優(yōu)勢克隆群均為CC5(71/133;28/60),其次為CC7(18/133;7/60)。樹狀聚類分析中,21對母嬰對子中共有19對各自聚成一類,與eBURST V3軟件分析得出的結(jié)果相似。結(jié)論該區(qū)域孕婦及新生兒人群中SA的攜帶率略低,但孕婦中MRSA菌株攜帶率略高。孕婦及新生兒中約65%及38%的SA呈現(xiàn)多藥耐藥,耐藥性嚴(yán)重,毒力基因的攜帶率較低。孕婦中MRSA以醫(yī)院來源為主,新生兒以社區(qū)來源為主。孕婦及新生兒中SA流行的ST型別為ST188、ST7和ST6,MRSA主要為ST59、ST6和ST188,與我國流行菌株接近,也與國際流行菌株存在密切關(guān)系。調(diào)整其他影響因素后,母親攜帶SA的新生兒攜帶SA的風(fēng)險是母親非攜帶的新生兒的6.90倍。
[Abstract]:Objective to explore the carrying rate of Staphylococcus aureus (Staphylococcus aureus, hereinafter referred to as SA) in pregnant women (vagina) and their neonates (oral, perinatal, ear and umbilical), to explore the drug sensitivity and molecular characteristics of SA, to study the homology of mother and infant SA and to predict the risk of maternal and infant transmission, and to provide a scientific basis for effective prevention and control measures. A prospective cohort study combined with molecular epidemiology was used to facilitate the sampling of pregnant women who were hospitalized and followed up. The pregnant women were divided into exposure groups according to the vaginal secretions of pregnant women (vaginal secretions separation and identification of SA positive) and non exposed groups (vaginal secretions isolated and identified SA negative). The outcome was the carrying rate of SA and relative risk ratio in the two groups of newborn babies born with SA. (relative risk, RR); the drug sensitivity analysis of SA using Kirby-Bauer test paper diffusion method and further identification of methicillin resistant Staphylococcus aureus (methicillin-resistant Staphylococcus aureus, MRSA) strains. Using the paper diffusion method and mecA gene amplification method, t test, x 2 test or Fisher exact probability were used to compare the difference of other groups in different groups, the difference between the risk factors of SA and MRSA and the drug sensitivity of the newborn were explored. The factors of the single factor analysis of P0.05 were integrated into the generalized linear model for multi factor analysis; the Kappa test score was used. Analysis of the consistency between the phenotype of mother and baby SA and the characteristics of the toxin gene; using the PCR technique to detect the toxin gene (PVL, TST, ETA and ETB), and the further SCCmec molecular typing of the MRSA strain; use the multipoint sequencing (multilocus sequencing typing, MLST) to explore the local epidemic type and determine the homology of the mother and child. 1834 pregnant women, 133 of the exposure group (SA positive) and 1701 in the non exposed group (SA negative), were followed up for a total of 1834 newborn samples of.SA and MRSA: 1834 pregnant women, 133 (7.25%) carrying SA, 31 (1.69%) carrying MRSA.1834 name neonates, 60 (3.27%) carrying SA, 15 (0.82%) carrying MRSA. exposure. The carrying rate of SA in the group of newborn infants was 15.79%, MRSA was 2.26%, the rate of SA carrying in the non exposed group was 2.29%, the SA carrying rate of newborn infants in 0.71%. two was different, the MRSA carrying rate was no difference. The relative risk ratio of SA in the exposed group was 6.89 times as much as that of the non exposed group (95%CI: 4.18-11.36), adjusting the sex of the newborn, the mode of delivery, and whether the fetus was born. The relative risk of premature rupture of membrane and the number of pregnant days was 6.90 times higher than that of the non exposed group (95%CI:4.22-11.27). A total of 21 pairs of mothers and infants detected SA positive at the same time. Drug sensitivity test: the resistance rate of SA to clindamycin (41.35%), erythromycin (50.38%), teicorin (81.20%) and penicillin (92.48%) was higher in pregnant women. Compared to the strains of methicillin-susceptible Staphylococcus aureus (MSSA), MRSA was a risk factor for multidrug resistance (OR=3.64; 95%CI:1.23-13.02). The resistance rate of neonatal SA to clindamycin (28.33%), erythromycin (46.67%) and penicillin (93.33%) was higher; MRSA was a risk factor for multidrug resistance (OR=12.36; 95). %CI:2.56-76.77). There was no difference in the drug sensitivity of SA in the exposed and non exposed neonates. The consistency of.21 to mother to child was statistically significant (P0.01), and the consistency was moderate (Kappa=0.523). The gene carrying rate of SA in pregnant women was 2.26%, 3.01%, 0% and 2.26%, and 5% and 3.33% in newborn infants. 11.67% and 0.00%. pregnant women and neonates with MRSA and MSSA carrying PVL, TST, ETA genes were not different from.21 to mother and baby, and the SA in mother and newborn was not detected in PVL and ETB genes. The consistency of mother and baby with TST and ETA genes was statistically significant. (0.462).SCCmec typing: among MRSA isolates from pregnant women, 45.16% (14/31) belong to hospital related MRSA (hospital-associated MRSA, HA-MRSA), and 29.03% (9/31) belong to community related MRSA (community-associated MRSA, CA-MRSA). RSA was dominated by SCCmec IV A (4/7) and type II (2/7). The resistance of HA-MRSA and CA-MRSA strains to clindamycin, erythromycin and penicillin were higher in pregnant women and neonates, and there was no statistical difference between the resistance and multidrug resistance of the 11 drugs. In the mother infant pair, 1 pairs of MRSA strains were detected and the same as SCCmec II.MLST: pregnant women. The main ST types of SA in the newborn were ST188 (37/133; 15/60), ST7 (18/133; 7/60) and ST6 (14/133; 5/60). A total of 19 pairs of child pairs were divided into one class, which was similar to the results obtained by eBURST V3 software analysis. Conclusion the carrying rate of SA in pregnant women and newborns in this region is slightly lower, but the carrying rate of MRSA strains in pregnant women is slightly higher. The SA of pregnant women and newborns about 65% and 38% of SA presents multidrug resistance, the drug resistance is serious and the carrying rate of virulence genes is low. MRSA is mainly hospital source, and the newborn is mainly community source. The ST types of SA in pregnant women and newborns are ST188, ST7 and ST6, MRSA mainly ST59, ST6 and ST188, which are close to the epidemic strains in our country, and are closely related to the international epidemic strains. 6.90 times as much as non - carrying newborns.
【學(xué)位授予單位】：廣東藥科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R714.251
本文編號：2150781
[Abstract]:Objective to explore the carrying rate of Staphylococcus aureus (Staphylococcus aureus, hereinafter referred to as SA) in pregnant women (vagina) and their neonates (oral, perinatal, ear and umbilical), to explore the drug sensitivity and molecular characteristics of SA, to study the homology of mother and infant SA and to predict the risk of maternal and infant transmission, and to provide a scientific basis for effective prevention and control measures. A prospective cohort study combined with molecular epidemiology was used to facilitate the sampling of pregnant women who were hospitalized and followed up. The pregnant women were divided into exposure groups according to the vaginal secretions of pregnant women (vaginal secretions separation and identification of SA positive) and non exposed groups (vaginal secretions isolated and identified SA negative). The outcome was the carrying rate of SA and relative risk ratio in the two groups of newborn babies born with SA. (relative risk, RR); the drug sensitivity analysis of SA using Kirby-Bauer test paper diffusion method and further identification of methicillin resistant Staphylococcus aureus (methicillin-resistant Staphylococcus aureus, MRSA) strains. Using the paper diffusion method and mecA gene amplification method, t test, x 2 test or Fisher exact probability were used to compare the difference of other groups in different groups, the difference between the risk factors of SA and MRSA and the drug sensitivity of the newborn were explored. The factors of the single factor analysis of P0.05 were integrated into the generalized linear model for multi factor analysis; the Kappa test score was used. Analysis of the consistency between the phenotype of mother and baby SA and the characteristics of the toxin gene; using the PCR technique to detect the toxin gene (PVL, TST, ETA and ETB), and the further SCCmec molecular typing of the MRSA strain; use the multipoint sequencing (multilocus sequencing typing, MLST) to explore the local epidemic type and determine the homology of the mother and child. 1834 pregnant women, 133 of the exposure group (SA positive) and 1701 in the non exposed group (SA negative), were followed up for a total of 1834 newborn samples of.SA and MRSA: 1834 pregnant women, 133 (7.25%) carrying SA, 31 (1.69%) carrying MRSA.1834 name neonates, 60 (3.27%) carrying SA, 15 (0.82%) carrying MRSA. exposure. The carrying rate of SA in the group of newborn infants was 15.79%, MRSA was 2.26%, the rate of SA carrying in the non exposed group was 2.29%, the SA carrying rate of newborn infants in 0.71%. two was different, the MRSA carrying rate was no difference. The relative risk ratio of SA in the exposed group was 6.89 times as much as that of the non exposed group (95%CI: 4.18-11.36), adjusting the sex of the newborn, the mode of delivery, and whether the fetus was born. The relative risk of premature rupture of membrane and the number of pregnant days was 6.90 times higher than that of the non exposed group (95%CI:4.22-11.27). A total of 21 pairs of mothers and infants detected SA positive at the same time. Drug sensitivity test: the resistance rate of SA to clindamycin (41.35%), erythromycin (50.38%), teicorin (81.20%) and penicillin (92.48%) was higher in pregnant women. Compared to the strains of methicillin-susceptible Staphylococcus aureus (MSSA), MRSA was a risk factor for multidrug resistance (OR=3.64; 95%CI:1.23-13.02). The resistance rate of neonatal SA to clindamycin (28.33%), erythromycin (46.67%) and penicillin (93.33%) was higher; MRSA was a risk factor for multidrug resistance (OR=12.36; 95). %CI:2.56-76.77). There was no difference in the drug sensitivity of SA in the exposed and non exposed neonates. The consistency of.21 to mother to child was statistically significant (P0.01), and the consistency was moderate (Kappa=0.523). The gene carrying rate of SA in pregnant women was 2.26%, 3.01%, 0% and 2.26%, and 5% and 3.33% in newborn infants. 11.67% and 0.00%. pregnant women and neonates with MRSA and MSSA carrying PVL, TST, ETA genes were not different from.21 to mother and baby, and the SA in mother and newborn was not detected in PVL and ETB genes. The consistency of mother and baby with TST and ETA genes was statistically significant. (0.462).SCCmec typing: among MRSA isolates from pregnant women, 45.16% (14/31) belong to hospital related MRSA (hospital-associated MRSA, HA-MRSA), and 29.03% (9/31) belong to community related MRSA (community-associated MRSA, CA-MRSA). RSA was dominated by SCCmec IV A (4/7) and type II (2/7). The resistance of HA-MRSA and CA-MRSA strains to clindamycin, erythromycin and penicillin were higher in pregnant women and neonates, and there was no statistical difference between the resistance and multidrug resistance of the 11 drugs. In the mother infant pair, 1 pairs of MRSA strains were detected and the same as SCCmec II.MLST: pregnant women. The main ST types of SA in the newborn were ST188 (37/133; 15/60), ST7 (18/133; 7/60) and ST6 (14/133; 5/60). A total of 19 pairs of child pairs were divided into one class, which was similar to the results obtained by eBURST V3 software analysis. Conclusion the carrying rate of SA in pregnant women and newborns in this region is slightly lower, but the carrying rate of MRSA strains in pregnant women is slightly higher. The SA of pregnant women and newborns about 65% and 38% of SA presents multidrug resistance, the drug resistance is serious and the carrying rate of virulence genes is low. MRSA is mainly hospital source, and the newborn is mainly community source. The ST types of SA in pregnant women and newborns are ST188, ST7 and ST6, MRSA mainly ST59, ST6 and ST188, which are close to the epidemic strains in our country, and are closely related to the international epidemic strains. 6.90 times as much as non - carrying newborns.
【學(xué)位授予單位】：廣東藥科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R714.251
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